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由卡介苗刺激的淋巴细胞上清液可以改变肿瘤的抗原性,并刺激同种异体 T 细胞反应。

Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses.

机构信息

Department of Oncology, Division of Clinical Sciences, St George's, University of London, 2nd floor, Jenner Wing, London SW17 0RE, UK.

出版信息

Br J Cancer. 2011 Aug 23;105(5):687-93. doi: 10.1038/bjc.2011.306. Epub 2011 Aug 9.

Abstract

BACKGROUND

Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis.

METHODS

In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines.

RESULTS

BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement.

CONCLUSION

These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility.

摘要

背景

人类白细胞抗原 1 类(HLA1)的表达减少通常是肿瘤逃避宿主免疫系统监测的一种机制。这通常与无法对疾病产生适当反应的免疫功能有关,这可能导致有利于致癌的状态。

方法

在目前的研究中,我们探讨了卡介苗(BCG)对白细胞细胞因子产生的影响,细胞因子是产生抗肿瘤作用的关键决定因素,还评估了这些细胞因子鸡尾酒对实体瘤细胞系中 HLA1 表达的影响。

结果

BCG 强烈激活了广泛的白细胞,并且还增强了 Th1 优势的细胞因子的产生。BCG 处理后的白细胞上清液显著增加了癌细胞系表面 HLA1 的表达,这与细胞毒性 T 细胞活性的增加相关。我们还表明,增加的 HLA1 表达与细胞内信号通路的激活相关联,这是由 Th1 细胞因子干扰素-γ和肿瘤坏死因子-α的增加触发的,因为抵消它们的作用否定了增强作用。

结论

这些研究通过白细胞的细胞因子修饰作用及其增强肿瘤可见性的能力,再次证实了 BCG 作为一种潜在的免疫疗法的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5088/3188926/00e432e99e2b/bjc2011306f1.jpg

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